The toxic side effects of chemotherapy and debilitation caused by radical surgery have prompted the search for homeostatic alternatives to conventional cancer therapeutic modalities. In view of the many similarities between embryonic development and neoplasia, one area of promise in this search is the possiblity that the malignant behavior of cells can be regulated by epigenetic mechanisms, as are the cells of the embryo. More specifically, when competent malignant cells are placed in an appropriate microenvironment or individuation field, they may pursue a normal developmental course and become benign. This work pursues the rationale behind the methods employed in exploring this possibility by using the morphogenetic properties of demineralized diaphyseal bone matrix to affect the growth and differentiation of a variety of transplantable rat tumors, including the Swarm rat chondrosarcoma. The specific aspects to be evaluated include in vivo modulation of tumor growth, tumor stem cell pluripotentiality, histogenetic specificity, hormonal regulation, developmental versus nonspecific growth regulation, and mesenchymal competence. In addition, we will develop an in vitro model in an attempt to elucidate the specific molecular natures of the inductors operative in the bone matrix/tumor cell interaction. In so doing, we hope to provide both fundamental insight into the mechanism of naturally occurring neoplasms and a clinically applicable method for the treatment of mesenchymal cancer. (M)